A new concept for the simultaneous detection of primary and secondary scintillation in time projection chambers is proposed. Its core element is a type of very-thick GEM structure supplied with ...transparent electrodes and machined from a polyethylene naphthalate plate, a natural wavelength shifter. Such a device has good prospects for scalability and, by virtue of its genuine optical properties, it can improve on the light collection efficiency, energy threshold and resolution of conventional micropattern gas detectors. This, together with the intrinsic radiopurity of its constituting elements, offers advantages for noble gas and liquid based time projection chambers, used for dark matter searches and neutrino experiments. Production, optical and electrical characterization, and first measurements performed with the new device are reported.
Hydroxychloroquine and azithromycin have been used to treat patients with coronavirus disease 2019 (Covid-19). However, evidence on the safety and efficacy of these therapies is limited.
We conducted ...a multicenter, randomized, open-label, three-group, controlled trial involving hospitalized patients with suspected or confirmed Covid-19 who were receiving either no supplemental oxygen or a maximum of 4 liters per minute of supplemental oxygen. Patients were randomly assigned in a 1:1:1 ratio to receive standard care, standard care plus hydroxychloroquine at a dose of 400 mg twice daily, or standard care plus hydroxychloroquine at a dose of 400 mg twice daily plus azithromycin at a dose of 500 mg once daily for 7 days. The primary outcome was clinical status at 15 days as assessed with the use of a seven-level ordinal scale (with levels ranging from one to seven and higher scores indicating a worse condition) in the modified intention-to-treat population (patients with a confirmed diagnosis of Covid-19). Safety was also assessed.
A total of 667 patients underwent randomization; 504 patients had confirmed Covid-19 and were included in the modified intention-to-treat analysis. As compared with standard care, the proportional odds of having a higher score on the seven-point ordinal scale at 15 days was not affected by either hydroxychloroquine alone (odds ratio, 1.21; 95% confidence interval CI, 0.69 to 2.11; P = 1.00) or hydroxychloroquine plus azithromycin (odds ratio, 0.99; 95% CI, 0.57 to 1.73; P = 1.00). Prolongation of the corrected QT interval and elevation of liver-enzyme levels were more frequent in patients receiving hydroxychloroquine, alone or with azithromycin, than in those who were not receiving either agent.
Among patients hospitalized with mild-to-moderate Covid-19, the use of hydroxychloroquine, alone or with azithromycin, did not improve clinical status at 15 days as compared with standard care. (Funded by the Coalition Covid-19 Brazil and EMS Pharma; ClinicalTrials.gov number, NCT04322123.).
This work summarises the results of calcium and magnesium ion removal from raw water feeding an industrial steam generation system. The cations were precipitated with sodium phosphate before ...separation of the solids by dissolved air flotation, with micro and nanobubbles. Studies were done at bench scale and validated at pilot scale (raw water feed = 1 m
3
h
−1
; air-to-solids ratio = 0.046 mg of air mg
−1
of solids; residence time = 11 min). Results indicated that chemical precipitation followed by flotation significantly improved the quality of the boiler water. Best results were obtained after precipitating the cations with 50 mg L
−1
of sodium phosphate at pH 11.5 and flotation with a saturation pressure (P
sat
) of 4 bar, a recycling ratio of 30% and a sodium oleate concentration of 20 mg L
−1
as an hydrophobizing reagent. The latter assisted the adhesion of the nanobubbles (100-500 nm) generated at 4 bar with a numeric concentration of about 2.5 × 10
8
NBs mL
−1
. At pilot scale, the total hardness in the solution decreased by 80%; the residual calcium and phosphate ion concentrations were 12 and 2 mg L
−1
respectively. This cell was designed including lamellae and perforate plate to improve the superficial loading capacity (up to 9 m h
−1
). The results were explained by chemical and interfacial phenomena and it is believed that this technique has great potential in water softening processes.
The calculated position resolutions for X-ray photons (1–60 keV) in pure noble gases at atmospheric pressure are presented. In this work we show the influence of the atomic shells and the detector ...dimensions on the intrinsic position resolution of the used noble gas. The calculated results were obtained by using a new software tool, Degrad, and compared to the available experimental data.
Pyriproxyfen is an insecticide used worldwide that acts as a biomimetic of juvenile hormone. This study investigated metabolic and synaptic impairments triggered by pyriproxyfen using zebrafish ...acetylcholinesterase (zbAChE) and mitochondria as markers. A brain zbAChE assay was performed in vitro and in vivo covering a range of pyriproxyfen concentrations (0.001–10 μmol/L) to assess inhibition kinetics. Docking simulations were performed to characterize inhibitory interactions. Zebrafish male adults were acutely exposed to 0.001, 0.01 and 0.1 μg/mL pyriproxyfen for 16 h. Mitochondrial respiration of brain tissues was assessed. ROS generation was estimated using H2DCF-DA and MitoSOX. Calcium transport was monitored by Calcium Green™ 5 N. NO synthesis activity was estimated using DAF-FM-DA. Brain acetylcholinesterase showed an in vivo IC20 of 0.30 μmol/L pyriproxyfen, and an IC50 of 92.5 μmol/L. The inhibitory effect on zbAChE activity was competitive-like. Respiratory control of Complex I/II decreased significantly after insecticide exposure. The MitoSOX test showed that O2− generation had a pyriproxyfen dose-dependent effect. Brain tissue lost 50% of Ca2+ uptake capacity at 0.1 μg/mL pyriproxyfen. Ca2+ release showed a clear mitochondrial impairment at lower pyriproxyfen exposures. Thus, Ca2+ transport imbalance caused by pyriproxyfen may be a novel deleterious mechanism of action. Overall, the results showed that pyriproxyfen can compromise multiple and interconnected pathways: (1) zbAChE impairment and (2) the functioning of the electron transport chain, ROS generation and calcium homeostasis in zebrafish brain mitochondria. Considering the many similarities between zebrafish and human, more caution is needed when pyriproxyfen is used in both urban and agricultural pest control.
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•A multilevel approach to pyriproxyfen neurotoxicity was performed.•In vitro exposure of zbAChE to pyriproxyfen showed competitive-like inhibition.•Brain O2$− production was dependent on the dose of pyriproxyfen;•Calcium transport was changed after pyriproxyfen exposure.•Pyriproxyfen showed that NOS activity is not a major route to cellular impairment.
Antimicrobial resistance (AMR) is considered one of the greatest threats to global health. Methicillin-resistant
(MRSA) remains at the core of this threat, accounting for about 90% of
infections ...widespread in the community and hospital settings. In recent years, the use of nanoparticles (NPs) has emerged as a promising strategy to treat MRSA infections. NPs can act directly as antibacterial agents via antibiotic-independent activity and/or serve as drug delivery systems (DDSs), releasing loaded antibiotics. Nonetheless, directing NPs to the infection site is fundamental for effective MRSA treatment so that highly concentrated therapeutic agents are delivered to the infection site while directly reducing the toxicity to healthy human cells. This leads to decreased AMR emergence and less disturbance of the individual's healthy microbiota. Hence, this review compiles and discusses the scientific evidence related to targeted NPs developed for MRSA treatment.
The lack of predictivity of animal's models has increased the failure rate of drug candidates. Thus, the reversion of this scenario using preliminary in vitro assays and metabolism prediction can ...reduce the unnecessary use of animals, as well as predict toxic effects at preclinical and clinical stages. The present study aimed to evaluate safety of four biologically active molecules (RN104, RI78, ICH, PCH) with potential therapeutic applications synthesized in our laboratory. Initially, we used MTT cytotoxicity against A549, H9C2, HepG2, LLC-PK1 and NEURO-2 cell lines. RN104 showed the lowest cytotoxicity and further studies were conducted with it. The neutral red (NR) test was performed according to OECD-129 and then acute toxicity test (OECD-423). According to NR results we administered at 300 mg/kg on animals; however, no toxic effect was observed, while 2,000 mg/kg resulted in the death of one animal per group. After, metabolism prediction studies, performed using both ligand-based and structure-based, suggests three potential metabolites. In silico results suggested that potential metabolites could be fast eliminated and, then, this could be an explanation for lower observed toxicity in in vivo experiments. The results showed limitations of the NR as a predictor of the initial dose for the acute toxicity study, which may be related to metabolism. Therefore, the combination of theoretical and experimental studies is relevant to a general understanding of new molecule's toxicity.
•Pre-In vivo assays, such as MTT and NR assays, can reduce unnecessary mice experiments when used in appropriated framework.•RN104 showed low cytotoxicity profile on cell-based assays.•RN104 proposed metabolites could indicate potential sites for further investigation.
A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) ...resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.
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